Anti-Aging from Superfoods and Modulating Skin Microbiota and Appearance. Philip Ludwig October 2018

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1 Anti-Aging from Superfoods and Modulating Skin Microbiota and Appearance Philip Ludwig October 2018

2 From profound intimacy Microbiota revolution Medicine Cosmetic Food and nutrition 2 to the market place

3 Microbiome trend in Personal care Industry A science-based skin care trend No longer just an acne focus Protection and prevention Fits both natural and dermocosmetic brand Word cloud created based on BASF big data analysis

4 Symbiosis / Dysbiosis HEALTHY SKIN EFFICIENT INNATE IMMUNE BARRIER EFFICIENT WOUND HEALING Antibiotics UV EFFICIENT PHYSICAL BARRIER SYMBIOSIS SYMBIOSIS COMFORTABLE SKIN Pollution SKIN MICROBIOTA INTERPLAY Excessive hygiene SENSITIVE SKIN REDNESS, DANDRUFF, ACNE DYSBIOSIS BARRIER DISRUPTION Dietary patterns IMPAIRED WOUND HEALING DRY SKIN INFLAMMATION Environmental and behavioral factors affect microbiota and create an imbalance

5 Cosmetic solutions Traditional approach- blemished skin Boost defense, protect barrier Beta-Hydroxyde ACSD, AHCare L65, AHCare G60 Betapur, PatcH20, Purisoft, Prebiotics Probiotics and Postbiotics Oligolin Relipidium An ecosystemic approach

6 Cosmetic Solutions ECOSYSTEM STRENGTHENS THE BARRIER ANTI-POLLUTION - PROTECTS MICROBIOTA FROM POLLUTION DEFENSES ANTI-MICROBIAL ACTION STIMULATES NATURAL SKIN CELL DEFENSE Approach TRADITIONAL PRE / PRO / POST-BIOTIC 6 Prolonged effectiveness of salicylic acid Much milder than a treatment with pure AHA Much milder than a treatment with pure AHA Prebiotic power of flax Healthy ecosystem promoter for dry skin Double line of defense against acne Comprehensive optimizer of urban skin health Microbiota anti-pollution shield

7 Cosmetic solutions Traditional approach- blemished skin Boost defense, protect barrier Prebiotics Probiotics and Postbiotics Beta-Hydroxyde ACSD, AHCare L65, AHCare G60 Betapur, PatcH20, Purisoft, Bix Activ, Phytosoothe Oligolin Relipidium An ecosystemic approach

8 Bix Activ The cutaneous diet for a pure and mattified skin

9 Three clinical signs solved with Bix Activ Less sebum production- The skin is mattified Less visible pores Less visible Imperfections 9 10/23/2018 Skin hydration preserved

10 Bix Activ helps reduce the activity of sebaceous gland for a mattifying effect Multi-ethnic solution Sebum production in vitro with Bix Activ 0.02% African American sebocytes: -28% With Bix Activ at 0.25% 56 days vs D0 in vivo Number of active pores reduced by : -53% Oily skin is linked to hyperactive sebaceous glands that produce excessive sebum Caucasian sebocytes: Asian sebocytes: -11% -17% Sebum excretion rate reduced by: -71% D0 D28 D56 Sebum production stimulated by HS Bix Activ at 0.02% Measure of sebum production with Sebutape method 10

11 Bix Activ acts like a cutaneous diet to block the signal inducing hyperkeratinization and avoid pores to appear bigger Our diet has an impact as well on keratinocytes due to IGF-1 production. IGF-1 stimulates the keratinocytes proliferation Bix Activ 0.05% in vitro Bix Activ stimulates IGFBP3 synthesis in keratinocytes to neutralize IGF-1 X1.7 Bix Activ 0.25% in vivo Pores 'size is decreased by 9% Excessive keratinization around pores Self assessment 86% 94% 86% Enlarged pores are favored by hyperproliferation of keratinocytes causing hyperkeratinization My skin pores looks minimized after using the product The product does not clog my skin's pores The product tightens pores on your face 11

12 In vivo In vitro Bix Activ action on skin imperfections P. acnes with Bix Activ at 0.02% P. acnes virulence: -68% 4 days 37 C in anoxia Without direct effect on bacteria growth Hemi-face treated with Bix Activ at 0.25% D0 D28 D56 Virulent bacteria secrete lipase that triggers inflammation and create imperfections BASF BCS BASF BCS BASF BCS Visible reduction of skin imperfections appearance with results already after 4 weeks of treatment 12

13 Bix Activ action on P. acnes lipase P. acnes P. acnes growth Lipase activity 4 days NS NS NS 37 C in anoxia Cell growth OD at 600 nm Supernatant centrifugated, lipase activity measured with Fluorescence read at 520/600 nm. Bix Activ doesn t modify P. acnes growth but inhibits its lipase activity. Bix Activ avoids the worsening of an oily skin and the appearance of imperfections 13

14 Description: Bixa orellana is an evergreen shrub up to 8 m high, it bears clusters of white to pink flowers, comparable to wild roses. The non edible fruits are in clusters of red-brown seed pods covered in soft spines. Each pod contains many seeds covered with a thin waxy red aril rich in carotenoids. At maturity, the pod dries, hardens, and splits open, exposing the seeds. Bixa orellana, The red lip tree INCI: Bixa orellana seed extract Family: Bixaceae Origin: Burkina Faso Species: Bixa orellana Plant part: Seed Native to tropical America but grows in other regions of South and Central America and Africa. Humid tropics Sunny places 0-20 deg. C mm annual precipitation Since ancient Mayan civilization, indigenous tribes of the South American rainforest have relied on Bixa Orellana's bright red annatto seeds for fabric dye, body paint and arts & crafts. In addition, tribes have long since believed that the seeds to work as an expectorant, and the roots to aid in digestion. For this reasons, native South Americans administer the whole plant as a natural medicinal treatment for bladder conditions, fevers, dysentery, burns, inflammation, heartburn and various skin problems. The fruits are collected from November to December on domesticated trees in the west part of Burkina Faso. Then the fruits are manually opened to release the seeds. The seeds are sun dried. BASF Partner sources the seeds from an historical supplier in Burkina Faso; it monitors the harvest with local independent farmers.

15 Bix Activ Product characteristics Bix Activ Description INCI Composition 100% BC10050 Standardized natural extract of Bixa Orellana seed, preservative free Maltodextrin (and) Bixa Orellana Seed Extract 50-70% Maltodextrin, 30-50% Bixa Orellana Seed Extract Dose of use 0.25% Aspect Solubility Preservative system Beige to yellowish fine powder Soluble in water None Naturalness content (ISO 16128) Regulatory data 100% natural origin PCPC IECSC IECIC 2015 JP cosmetics QD additive 15

16 Bix Activ Stability & Formulation Storage conditions Formulation method In its original packaging and protected from moisture, light and heat, at C Shelf life: 24 months Dissolved at 20% w/w in water at room temperature and then incorporated during the final process below 30 C, or at room temperature for cold processing. Optimal ph: 3 8 BASF BCS 16

17 Phytosoothe Natural protection for the physical and microbiotic skin barrier Active ingredient

18 Structural similarities of phytosterols Cholesterol b-sitosterol Campesterol Brassicasterol The important role of cholesterol in human skin Stabilization of the phospholipid bilayers in human cell membranes Major component of the stratum corneum lipidic cement Helps maintenance of a proper physical skin barrier function, together with ceramides and fatty acids Naturally occurring phytosterols Stabilization of the phospholipid bilayers in plant cell membranes Anti-inflammatory activity Natural sourcing from vegetal oils; also present in other foods such as cereals, vegetables, fruit and berries Widely used as food additives for cholesterol-lowering foods

19 Phytosoothe Rapeseed oil 1 Sterols separation 2 Purification Purified sterols (>95%) * 3 Mixing with Cetearyl Alcohol 4 Prilling Phytosoothe 40-60% 25-40% 7-18% Purified natural rapeseed phytosterols Easy to handle product with low melting point of C (pure phytosterols: C *) Preservative free Excellent safety profile; components well-known from food and topical applications NOAEL** value available for both components * 100% Brassica Campestris (Rapeseed) Sterols are also available under the reference Generol R ** No Observed Adverse Effect Level Rapeseed origin: Europe

20 Skin homeostasis through barrier function Physical barrier Microbiotic barrier Horny layer made of dead corneocytes and intercellular lipids Skin microbiota made of bacteria, viruses and archea Prevention of penetration of external components Physical Microbiotic Prevention of colonization by pathogenic bacteria Limitation of water evaporating from the skin Education and stimulation of skin defense to evade pathogenic

21 Skin microbiota Taxonomic investigation High level Domain Kingdom Phylum 16S rdna gene sequencing Advanced bacterial identification method Classification Class Order Low level Family Genus Species

22 Skin microbiota Taxonomic investigation after detergent application High level Classification Low level Domain Kingdom Phylum Class Order Family Genus Species BASF study 16S rdna gene sequencing 0.5% of a SLS patch applied on the back 24 hrs Patch removal 24 hrs Skin microbiota sampling 24 hrs 16S metasequencing and computational analysis

23 New scientific results Disruption of microbiota balance by hygiene products Skin microbiota after detergent application Genus level Microbiota before SLS patch application Microbiota after SLS patch application Opportunistic pathogenic microorganisms Resident commensal microorganisms Pseudomonas x2 (p<0,1) Pantoea x117 (p<0,05) Micrococcus -39% (p<0,05) Corynebacterium -42% (p<0,05) Paracoccus -36% (p<0,01) Hygiene products can disrupt the microbiotic skin barrier

24 The Challenge Strengthen the restoration of the skin s physical and microbiotic barrier For protection and repair of fragile skin and scalp

25 Phytosoothe Physical barrier restoration - Results Clinical study after occlusive SLS patch at D-2 for 24 hours, then 7 days of treatment with or without 2% Phytosoothe in body oil vehicle [ formulation] TEWL after SLS damage Hydration after SLS damage Unrepaired barrier Barrier repair with 2% Phytosoothe Unrepaired barrier Barrier repair with 2% Phytosoothe TEWL value D-2 D7 (***)/D-2 Unrepaired damages after 7 days Statistics: Mean on 23 volunteers Wilcoxon or Student t test (*) p<0.05 (***) p<0.001 Corneometer value D-2 D7 Unrepaired damages after 7 days (***)/D-2 Statistics: Mean on 23 volunteers Wilcoxon or Student t test (***) p<0.001 Phytosoothe strengthens the skin barrier function and helps to repair and rehydrate impaired skin

26 Phytosoothe Microbiotic barrier restoration Investigated microorganisms Resident commensal microorganisms ( good ) Opportunistic pathogenic microorganisms ( evil ) Micrococcus Paracoccus Corynebacterium Pseudomonas Pantoea Produces DNA repairing enzymes Can metabolize pollutants (use of biphenylated compounds as carbon source) Can metabolize pollutants (use of propylene glycol as carbon source) Produces antimicrobial peptides Certain species (Corynebacterium striatum) can decrease the virulence of Staphylococcus aureus Can produce metabolites that degrade lipids on skin (skin barrier impairment) Known as environmental pathogenic Very limited occurrence on human skin Significant decrease after SLS application Significant increase after SLS application

27 Phytosoothe Microbiotic barrier restoration Results Microbiota clinical study after occlusive SLS patch at D-2 for 24 hours, then 7 days of treatment with 2% Phytosoothe in body oil vehicle Restoration of abundance of resident commensal Micrococcus Corynebacterium Paracoccus +66% % +46% Phytosoothe helps the recovery of resident commensal microorganisms after barrier impairment

28 Phytosoothe Microbiotic barrier restoration Results Microbiota clinical study after occlusive SLS patch at D-2 for 24 hours, then 7 days of treatment with 2% Phytosoothe in body oil vehicle Cutback of the growth of opportunistic pathogens Pantoea Pseudomonas -89% % Phytosoothe helps to decrease potential pathogens after barrier impairment

29 Barrier impairment of the scalp Concerned scalp conditions Sensitive scalp Dry scalp Dandruff Harsh hair treatments Hair straighteners Hair relaxers Highly alkaline products Common in ethnic hair care Symptoms Scalp irritation Scalp itching Scalp tingling Hair damage

30 Barrier impairment in baby care Characteristics of baby skin Fragile; barrier function still immature Babys stratum corneum is thinner than of adults (on average 30%) Higher TEWL Less sebum production Tendency to dryness and irritations

31 Phytosoothe Conceivable claims * Helps to restore the physical skin barrier after impairment 1) Reduces water loss by evaporation and increases hydration after barrier impairment 1) Particularly suitable for aggressed, dry and irritated skin and scalp 1) Soothes itching scalp 1) Helps to protect the fragile skin barrier of babies 3) Helps to restore the microbiotic skin barrier after impairment 1) Contributes to the cutback of the grown pathogen microflora after skin impairment 1) Supports the beneficial microflora recovery after skin impairment 1) Restores skin microbiota balance after disruption 1) * Assessment of local legislation and competition law is mandatory for the distributor of the cosmetic product. 1 In vivo results

32 Phytosoothe LS 9766 Characteristics & regulations Phytosoothe LS 9766 b-sitosterol Description INCI Easy to use rapeseed phytosterols with low-melting point Brassica Campestris (Rapeseed) Sterols (and) Cetearyl Alcohol CAS No ; Composition 100% Brassica Campestris (Rapeseed) Sterols: 50% ; Cetearyl Alcohol: 50% Preservatives None Campesterol Phytosoothe phytosterols Brassicasterol Naturalness (ISO 16128) - Pending - Appearance White colored powder of weak odor Solubility Insoluble in water; soluble in fatty phase at 60 C Use level Regulatory data 0.5-1% in shampoo, 1-3% in conditioner and skin care PCPC IECSC IECIC 2015 REACH JP cosmetics QD additive x

33 Phytosoothe Stability & Formulation Storage conditions Formulation method Shelf life: 2 years Storage temperature: C Store protected from heat and moisture Add in the fatty phase of emulsions at 80 C or in a part of surfactant solution previously heated at 60 C for shampoo (ph: 3-11) Phytosoothe LS 9766 Phytosoothe LS 9766 at 3% in a body lotion Phytosoothe LS 9766 at 0.5 % in a shampoo Use level: 0.5-1% in shampoo, 1-3% in conditioner and skin care Also available: Generol R,100% rapeseed sterols, with higher melting point.

34 Consumer and Market drivers Skin and Hair care Ingredients Hero Ingredients - Superfoods & Recognizable Naturals kale, broccoli, apple, blackberry, flax, moringa, fermented ingredients, seaweeds Exotic Influences from Asia, Africa, South America Green tea, Mushroom, Argan, Charcoal, passion fruit, etc, DIy Ingredient scrutiny Free From Parabens/Sulfate/Silicone/Mineral Oil/Animal-Ingredients/Gluten Sustainable and responsible sourcing Fair trade, community, food miles, transparency, social responsibility

35 SUPERFOOD INFUSION IN SKIN/HAIR CARE Farm to Face Super Seed therapy Super Fruit superpower Puricare Purisoft Oligolin Sqisandryl Litchiderm Treasure from the blue zone Ultimate Seaweeds Miraculous Food Transformation! Supreme Fermentation SlimExcess Shadownyl Relipidium Phytokine 35 BASF Personal Care

36 SUPERFOOD INFUSION IN SKIN/HAIR CARE Farm to Face Super Seed therapy Super Fruit superpower Puricare Purisoft Oligolin Sqisandryl Litchiderm Treasure from the blue zone Ultimate Seaweeds Miraculous Food Transformation! Supreme Fermentation SlimExcess Shadownyl Relipidium Phytokine 36 BASF Personal Care

37 Sqisandryl Skin revitalizer from superfruit berries

38 Schisandra: Traditionally known berries not yet in the Western hemisphere? Use in food Teas, juices, wines and sweets Food additive Functional food, superfood Food supplement Use as Adaptogen Helping the organism to adapt and resist to different kinds of stress Use in TCM Schisandra is considered particularly special among the medicinal herbs Proper species in TCM is Northern Schisandra Schisandra chinensis, considered superior to Southern Schisandra Schisandra sphenanthera

39 五行 - Wu Xing: Chinese five elements theory Wŭ wèi zǐ: The five flavor berry bitter sour Flavors sweet salty spicy Fivefold conceptual scheme that many traditional Chinese fields use to explain a wide array of phenomena

40 Use in food supplements and as superfood Schisandra chinensis berries Postage stamp from Russia showing Schisandra

41 Sqisandryl : Ecofriendly extraction process Natural, 100% Schisandra Chinensis Fruit Extract Adjuvant & preservative free (mono-component) Oil soluble Cosmos approved Condensator CO 2 tank Raw material (Schisandra chinensis berries) Extractor Separator Eco-friendly process Compressor Heating CO 2 extract Sqisandryl Non-water based Without any solvents With recycling of CO 2 CO 2 from natural springs in the German volcano Eifel region Non-destructive & selective CO 2 - gaseous CO 2 - supercritical CO 2 - liquid CO 2 supercritical + extract

42 Sqisandryl : Ecofriendly extraction process Schisandra chinensis berries Schisandrins 5-10 % Schisandrins Other unsaponifiables Triglycerides Free fatty acids Typical phytochemical composition of Sqisandryl (based on 2 industrial batches)

43 Sqisandryl Skin flexibility when exposed to mechanical force Immediate elasticity Elasticity recovery Gross elasticity 0.3% Sqisandryl Placebo Statistics: Percentage on 17 volunteers Student t test ( ) p<0.1 limited (*) p<0.05 (***) p<0.001 Sqisandryl improves immediate skin elasticity by up to 47%

44 Sqisandryl Volunteers subjective evaluation Self-evaluation of fine lines Illustrative images Sqisandryl improves fine lines

45 Sqisandryl Volunteers subjective evaluation Self-evaluation of fine lines Illustrative images Sqisandryl improves fine lines

46 Elasticity >20% improvement after 28 days Energy +42% ATP on fibroblasts Sqisandryl Vitality +49% proteins on fibroblasts Sqisandryl Stimulates ATP synthesis Stimulates protein synthesis Stimulates inner cohesion protein collagen XVII 氣 Enforcement of Qi Helps the skin to adapt to the impact of Free radicals, 19% reduction in ROS Pollutants Mechanical forces Adaptogen Tonicity, smoothness visible improvement after 28 days Fine lines visible reduction after 28 days Eco-friendly manufacturing process Non-water based Without any solvents With recycling of CO2

47 Sqisandryl Characteristics LS 9905 Sqisandryl Description Aspect Solubility Preservative system Schisandrins-titrated oil extract of Schisandra berries, obtained through CO 2 supercritical extraction Yellow to orange oily liquid, with characteristic odor Soluble in oils and glycerides None INCI Natural label Naturalness content (ISO 16128) Dose of Use 0.3% Schisandra Chinensis Fruit Extract Cosmos approved 100% natural origin Specifications Sum of Schisandrins (5-10%) Schisandra chinensis Berries Tracer(s) / Biomarker(s) Regulatory data Main Schisandrins: Schisandrol A, Schisandrol B, Schisandrin A, γ-schisandrin, Gomisin C PCPC IECSC IECIC* 2015 REACH JP & QD additive x * The ingredient is listed in IECIC 2015 as Schizandra Chinensis Fruit Extract

48 Sqisandryl Stability & Formulation Storage conditions Formulation method In its original packaging and protected from moisture and light, at 4 C Shelf life: 12 months Incorporate during the final process below 40 C, or at room temperature for cold processing. ph: 4 8

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